Advantage Topical Liquids for Fleas, Ticks, and Heartworms in Dogs and Cats

Medically Reviewed by Joshua Conrad, PharmD on October 20, 2024
Written by Kathleen Claussen, DVM
9 min read

The Advantage line of products (manufactured by Elanco) includes topical products (products that are applied to the skin) for prevention and treatment of fleas at all life stages, prevention of lice infestations, prevention of heartworm infection, treatment and control of certain types of mange, treatment and control of intestinal parasites (hookworms, roundworms, and whipworms), and treatment and control of ear mites, depending on the product being used. 

The Advantage topical liquid product line includes three product brands: Advantage XD, Advantage II, and Advantage Multi. Advantage Multi products are approved by the FDA for various antiparasitic uses in dogs, cats, and ferrets. Advantage II products are approved by the Environmental Protection Agency (EPA) for treatment and control of external parasites in dogs and cats. Advantage XD is only EPA-approved for fleas in cats.

Advantage XD topical liquid for cats contains the active ingredient spinetoram. Spinetoram is classified as a semi-synthetic, second-generation derivative of the natural insecticide spinosad. Spinetoram is used for the prevention and treatment of flea infestations in cats. Advantage XD is a topical liquid lasting eight weeks for the prevention and treatment of fleas in cats and kittens at least 8 weeks old and weighing at least 1.8 pounds (0.8 kilograms).

Advantage II and Advantage Multi products contain imidacloprid. Imidacloprid is a neonicotinoid insecticide that controls fleas and lice.

Advantage II products also contain pyriproxyfen. Pyriproxyfen is an insect growth regulator that helps to control fleas and prevent them from returning. 

Advantage II for Cats is a monthly (every 30 days) topical liquid labeled for treatment and prevention of fleas in cats. Advantage II for Dogs is a monthly (every 30 days) topical liquid labeled for treatment and prevention of fleas and lice in dogs. Cats and kittens need to be at least 8 weeks old and weigh at least 2 pounds (0.9 kilograms) to use Advantage II for Cats. Dogs and puppies need to be at least 7 weeks old and weigh at least 3 pounds (1.3 kilograms) to use Advantage II for Dogs. Even though they contain the same active ingredients, Advantage II for Dogs should not be used in cats and vice versa.

In addition to imidacloprid, Advantage Multi products also contain moxidectin. Moxidectin is classified as a macrocyclic lactone antiparasitic that is used to prevent heartworm disease and to treat intestinal roundworms and hookworms. 

Advantage Multi for Cats is a monthly topical liquid labeled for prevention of heartworm disease, killing adult fleas, and treatment of flea infestation. It is also approved for treatment and control of ear mite infestations and intestinal parasite infections (hookworms and roundworms). Cats and kittens need to be at least 9 weeks old and weigh at least 2 pounds (0.9 kilograms) to use Advantage Multi for Cats. 

Advantage Multi for Cats can also be used to prevent heartworm disease, kill adult fleas, and treat flea infestations in ferrets. Only the 0.4 milliliter (mL) Advantage Multi for Cat tubes can be used for ferrets. The other sizes would result in giving the animal too much or too little medicine. Ferrets should weigh between 2 pounds (0.9 kilograms) and 4.4 pounds (2 kilograms).

Advantage Multi for Dogs is a monthly topical liquid labeled for prevention of heartworm disease, treatment of circulating microfilariae (immature heartworms), killing adult fleas, and treatment of flea infestations. It is also approved for treatment and control of sarcoptic mange and treatment and control of intestinal parasite infections (hookworms, roundworms, and whipworms). Dogs and puppies need to be at least 7 weeks old and weigh at least 3 pounds (1.3 kilograms) to use Advantage Multi for Dogs.

There are some other uses for Advantage Multi for Dogs, including treatment of other types of mites in dogs. These uses are “extra-label” or “off-label,” meaning that there is evidence of safe and effective use, even if FDA approval has not been received for the specific use or animal.

Advantage products are usually well tolerated in animals. There is minimal risk for overdose, side effects, or drug interactions if used as labeled or as directed by your veterinarian.

Advantage XD and Advantage II products are available without a prescription. Advantage Multi products are available from your veterinarian or with a prescription from your veterinary pharmacy. 

Advantage II and Advantage Multi products are liquids that you apply to your pet’s skin between the shoulder blades once a month (every 30 days). Advantage XD is also a liquid applied to your cat’s skin, but it only needs to be used every eight weeks. 

To apply Advantage XD, make sure the skin at the base of the cat’s head is dry and healthy. Using the appropriate tube of Advantage XD, hold the applicator upright and twist the nozzle tip to open the tube. Then part the hair and squeeze the entire contents of the tube two to four times directly onto the skin. Do not touch that area until it is completely dry. Do not allow your cat or other pets in the household to groom (rub or lick) the application site until it dries.

To apply all other Advantage topical products (Advantage II and Advantage Multi), remove one tube that is the appropriate dose for the weight and animal (dog or cat). Hold the tube upright and remove the cap. Turn the cap over and push the other end into the tip of the tube to break the seal. Then part the pet’s hair until you can see the skin and squeeze the contents onto the skin as directed by the package label. This may be in one spot or several spots depending on the size of the animal. Do not touch that area until it is completely dry. Do not allow your pet or other pets in the household to groom (rub or lick) the application site for at least 30 minutes or until it dries.

Always follow your veterinarian’s directions for giving medicines to animals. Remember to tell your veterinarian about any medicines, vitamins, supplements, or herbal therapies that you are giving your pet. Talk to your veterinarian before stopping any pet medicines. 

  • Advantage II and Advantage XD products do not require a veterinary prescription to purchase.
  • Advantage II products start killing fleas within 12 hours and last for 30 days.
  • Advantage XD provides eight weeks of flea treatment for cats.
  • Advantage XD starts killing fleas in as little as 30 minutes.
  • Advantage Multi kills fleas through contact so the fleas do not have to bite the animals to die.
  • All Advantage products are topical solutions applied to the skin, so you do not have to make your pet swallow the medicine.

You and your veterinarian should monitor your pet for signs that the medicine is working (absence of live fleas), as well as for side effects of the medicine. There is no routine lab monitoring needed with Advantage products.

If Advantage Multi is used for intestinal parasites, follow-up fecal (stool) tests may be checked. If Advantage Multi is used for ear mites, follow-up ear tests may be done by your veterinarian. 

If Advantage Multi is used for skin mite treatment, your veterinarian will monitor for improvement of symptoms (like hair loss and itching) as well as perform periodic skin tests. 

Before applying Advantage Multi for Dogs, dogs need to have a negative heartworm test. The heartworm test should then be repeated yearly. If there are missed doses of Advantage Multi for Dogs, a heartworm test should be repeated before restarting the medication and then again in six months. Before giving Advantage Multi for Cats for heartworms, your veterinarian may test for the presence of existing heartworm disease if the cat is more than 6 months old.

Do not use an Advantage product in an animal that is allergic to its ingredients. Do not use Advantage products in dogs or cats below the minimum age or weight on the product label. Do not use cat products on dogs and do not use dog products on cats. Use them with caution in older, sick, or underweight dogs and cats. Use Advantage products with caution in cats that already test positive for heartworms or have an unknown heartworm status. Do not use Advantage Multi for Cats on sick or debilitated ferrets. Do not allow your pet or their housemates to lick the application site of Advantage products until dry (or for at least 30 minutes). Use Advantage products with caution in pregnant, nursing, or breeding animals.

Your pet should not be able to lick the site of application if using any of the Advantage topical products. Other pets may try to groom or lick at the application site, especially cats that clean each other. Try to prevent this from happening, especially for 30 minutes after application or until the skin is dry. If your pet ingests the medicine, they will usually have excessive salivation (drooling) and may even foam at the mouth. If your pet starts acting strangely, seek veterinary care.

Side effects are uncommon with Advantage products if they are used as directed on the label. Your pet may experience hair loss, hair change (greasy, clumping, or matting), redness, itching, or other signs of discomfort at the application site. If any of these symptoms occur, bathe your pet with mild soap and rinse with large amounts of water. 

Other side effects with Advantage XD and Advantage II products may include:

  • Vomiting
  • Diarrhea (loose stool)
  • Excessive drooling
  • Inactivity
  • Decreased appetite
  • Unusual behavior

Other side effects with Advantage Multi for Cats may include excessive sleeping or trouble waking up.

Other more serious side effects with Advantage Multi for dogs may include the following. Dogs with the MDR1 genetic mutation may be more sensitive to these side effects.

  • Depression
  • Big (dilated) pupils
  • Weakness or stumbling
  • Panting
  • Generalized muscle tremors

If you think that your pet is having a serious side effect or may have been overdosed, call your veterinary clinic immediately. If it is outside of regular office hours, you may contact a local emergency veterinary hospital or an animal poison control center. 

You can reach the ASPCA Animal Poison Control Center at 888-426-4435 or the Pet Poison Helpline at 855-764-7661.

Using multiple medicines can sometimes change how your pet’s medicines work or increase your pet’s risk for serious side effects. Always tell your veterinarian about any prescription or over-the-counter (OTC) medicines, vitamins/minerals, herbal products, and other supplements that your pet is using.

There are no reported drug interactions at this time.

  • Keep Advantage products out of the reach of children.
  • Wash your hands with soap after handling Advantage products.
  • Do not handle Advantage products if you are allergic to any of the ingredients.
  • Avoid getting Advantage topical liquid in your eyes or on your skin and clothing.
  • Avoid contact with the area of application of Advantage product on your pet until it is dry.

Advantage products are well tolerated by animals and the risk of an overdose is low. If you are concerned your pet is having an adverse reaction or if you suspect your pet has gotten more medicine than intended, call your veterinarian or veterinary emergency clinic immediately.

If your poet misses a dose, give the dose when you remember and then restart the dosing interval from that date. Do not double the dose of the medicine. 

If more than eight weeks have passed since the last dose of Advantage Multi, start the monthly topical liquid again. Your dog will need to have a heartworm test performed in six months to determine if there is heartworm disease. It takes six months from the bite of an infected mosquito till a dog may test positive for heartworm disease.

Store Advantage products in the original packaging in a cool, dry place. Store Advantage Multi products specifically between the temperatures of 39 and 77 F (39 to 25 C), avoiding excess heat or cold.